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to any anti psychotic. 11Anti psychotics are often used inpatients with Parkinson’s disease (PD) forthe management of psychotic symptoms,such as hallucinations. 12 In this group itis particularly important to avoid antipsychoticsor dosages of anti psychoticsthat can cause EPS. Clozapine has beenshown to be beneficial in several clinicaltrials, without worsening PD. 12-14 Olanzapinewas found to have limited efficacyin patients with PD for the managementof psychotic symptoms while potentiallyworsening their PD symptoms. 15,16Although quetiapine did not appear toworsen PD symptoms in studies, it alsodid not demonstrate significant improvementin psychotic symptoms. 17-19Patients with dementia with Lewybodies (DLB), which has parkinsonianfeatures in addition to those of dementiaand accounts for up to 20% of dementiacases, 20 are more sensitive to antipsychotics.In addition to progressive cognitivedecline, features of DLB includefluctuating cognition, recurrent visual andother types of hallucinations, spontaneousmotor features of parkinsonism, falls,syncope and systematized delusions. 21 Thetypical anti psychotics should not be usedin this population as they have been associatedwith severe and sometimes fatalsensitivity in at least 50% of patients withDLB. 22 Symptoms of this sensitivity includesudden sedation, increased confusion,rigidity, decreased mobility, and autonomicdisturbances like neuroleptic malignantsyndrome. 22 This sensitivity can also occurwith atypical anti psychotics. 22In the elderly population, anticholinergicmedications can worsen cognitiveimpairment in the presence of dementia.The low-potency typical anti psychotics,such as chlorpromazine should be avoidedin the elderly because they tend to be morelikely to cause anticholinergic effects. 11ceAntipsychotic use in the elderlyce lessonPharmacy Practice national continuing education programDosing considerationsin the elderlyWith aging, a number of physiologicchanges occur that can impact on medicationdisposition. Some of these changescan specifically affect anti psychotics. Anincrease in fat-to-muscle ratio can leadto accumulation of lipid-soluble medicationssuch as haloperidol. A reduction inthe synthesis of drug-binding proteins(e.g., albumin) in the elderly person canlead to a larger unbound drug concentrationfor highly protein-bound drugs (e.g.,haloperidol, risperidone, chlorpromazineand thioridazine). 23 With aging, bothhepatic and renal metabolism can bereduced and this may result in a longerduration of action of anti psychotics. Also,elderly people are more likely to experiencecentral nervous system adverseeffects of anti psychotics as a result of agreater ability of medication to cross theblood-brain barrier. 23 Table 2 outlinesdosing recommendations for selected antipsychoticsused to treat BPSD in theelderly.Some dosing recommendations for theuse of anti psychotics in dementia from aworking group of the American PsychiatricAssociation include: 6• Start at a low dose (e.g., risperidone0.25 mg per day) and use the lowesteffective dose.• Avoid rapid dose titration to minimizeadverse effects.• Reduce the dose if adverse effects areexperienced by the patient.• Use regularly scheduled doses rathertable 2NOWFREE!than as needed.• Use other treatments (e.g., non-pharmacologicalstrategies) if symptoms areirregular.Most anti psychotics can be given oncedaily. However, each patient’s symptomsshould be assessed individually to determinethe most optimal dosing.Adverse effect profilesAdverse effects of anti psychotics largelydepend on receptor affinities, in combinationwith patient factors, such as age.Depending on the drug, typical antipsychoticsgenerally have greater affinitiesfor D 2receptors, and less formuscarinic, adrenergic, serotonergic andhistaminic receptors. On the other hand,atypicals generally have weaker affinitiesfor D 2but more so for muscarinic, adrenergic,serotonergic and histaminic receptors.23 Table 3 compares anti psychoticswith respect to their relative receptoraffinities.Identification of the type of receptoractivity of an anti psychotic can help clinicianspredict which adverse effects aremore likely to occur. A high amount ofdopaminergic activity (especially antagonismat D 2) can cause extrapyramidaleffects. Muscarinic receptors are associatedwith anticholinergic effects. Alpha-1adrenergic receptor activity can includeorthostatic hypotension, arrhythmia andDosing of some antipsychotics in the elderly 9,10,25Antipsychotic Available dosage forms Behavioural disturbanceswith dementia*haloperidol tablet, injection, depot injection 1.5–2 mgperphenazine tablet 2–24 mgrisperidonetablet, liquid, oral disintegrating tablet,depot injection0.25–2 mgquetiapine tablet, long-acting tablet 25–150 mgclozapine tablet 6.25–50 mgolanzapine tablet, rapid-dissolving wafer, injection 5–7.5 mgziprasidone capsule N/A***Note: dose is total daily dose.** This medication has just been approved in Canada so there is limited experience in dementia and like most otherantipsychotics, it is not officially approved for behavioural disturbances.answer online at pharmacygateway.caseptember 2008 | pharmacypractice CE3

ce lessonNOWFREE!table 3Pharmacy Practice national continuing education programAntipsychotic use in the elderlyAntipsychotic receptor affinities 3,25,48-52Agent D 1D 2M 1α 15HT 2H 1chlorpromazine weak high mod erate high mod erate mod erateclozapine mod erate high very high very high very high very highhaloperidol none very high none weak weak noneuse of adjunctive therapies (e.g. amantadineand nizatidine) to manage weight gainassociated with anti psychotics. 30 Furtherstudy, particularly in an older populationat higher risk of type 2 diabetes, is requiredto determine the most effective and safestmanagement of weight gain due to antipsychoticsin older adults.olanzapine weak mod erate mod erate weak very high highquetiapine weak mod erate weak mod erate mod erate mod eraterisperidone none high none high very high highziprasidone n/a high very low low high lowD 1= dopamine type 1 receptor; D 2= dopamine type 2 receptor;M 1= muscarinic receptor; α 1= alpha-adrenergic receptor; 5HT 2= serotonin receptor; H 1= histamine 1 receptortremor. Weight gain is an example of aserotonergic effect of an anti psychotic.Histaminic effects include sedation,hypotension and weight gain. 23Clozapine can cause agranulocytosis,and may lower the seizure threshold withdosage increases greater than 100 mg perday, or at high doses (greater than 600 mgper day). 23 Clozapine is less likely to beused in the elderly (and other patients)due to its high risk-benefit ratio.Extrapyramidal symptomsAll anti psychotics have the potential tocause EPS, but the degree to which thisoccurs depends on the specific agent,receptor affinities and dose. Some studieshave shown there is a similar incidenceof EPS in patients taking atypical antipsychoticsand those prescribed low tomoderate doses of high-potency agents(e.g., haloperidol) or low-potency agents(e.g., chlorpromazine). 24,25 The incidenceof EPS increases with higher doses ofatypical anti psychotics. 24,25 EPS mayinclude parkinsonism, tardive dyskinesia,akathisia and acute dystonia. Table 4outlines the key features of each EPS.Anticholinergic effectsMost anti psychotics (except risperidoneand haloperidol) have affinity for muscarinicreceptors, which are a type of cholinergicreceptor. Blockade of these receptorscan lead to classic anticholinergic sideeffects such as tachycardia, dry mouth,blurred vision, constipation, urinary retentionand confusion. Of the atypical antipsychotics,clozapine and olanzapine havethe highest likelihood of anticholinergiceffects. Clozapine, however, may haveparadoxical effects such as urinary frequencyat higher doses and hypersalivationeven at lower doses. 26 Chlorpromazine andother low-potency typical anti psychoticsalso have affinity for muscarinic receptors.It is important to limit the use of any medicationwith anticholinergic effects in theelderly, particularly in those with dementia,especially since this increases the riskof cognitive decline. 27,28Weight gainMany anti psychotics have been associatedwith weight gain. The literature supportsthe greatest risk of weight gain with clozapineand olanzapine, less with quetiapineand low-potency typical anti psychotics andstill less with risperidone and high-potencytypical anti psychotics. 25 Weight gain maybe associated with anti psychotic affinity forthe H 1receptor and tends to occur in thefirst four to 12 weeks of treatment, particularlywith the atypical anti psychotics. 27,29 Apatient’s weight status should be consideredand monitored when determining the appropriatenessof an anti psychotic agent.There is limited evidence to support theDiabetesEpidemiologic data have linked the incidenceor exacerbation of diabetes to theuse of certain atypical anti psychotics. 31In most cases, hyperglycemia manifestedabout six weeks after beginning antipsychotictherapy, and was reversiblewhen the drug was removed. 32 Most casesof diabetes have been reported with clozapineand olanzapine. 32As a result of the potential impact ofatypical anti psychotics on weight, bloodglucose and lipids, the American DiabetesAssociation has published a consensus onrecommended monitoring for all patientson atypical anti psychotics. Patients shouldhave a baseline assessment of body massindex (BMI), waist circumference, bloodpressure, fasting plasma glucose, fastinglipid profile and family and personal history.Weight, fasting plasma glucose, fastinglipid profile and blood pressure shouldbe reassessed at regular intervals throughoutthe course of therapy. 33table 4EPS descriptions*EPS TypeparkinsonismtardivedyskinesiaakathisiaacutedystoniaDescription*Adapted from reference 25EPS = extrapyramidal symptomsbradykinesia, rigidity,tremor, posturalinstabilityrepetitive involuntarymovements (e.g. lipsmacking, grimacing,limb movements)restlessness andanxious agitationacute musclehypertonicity or spasmCE4 pharmacypractice | september 2008answer online at pharmacygateway.ca

DyslipidemiaSome studies have shown that certainanti psychotics cause hypertriglyceridemiaand result in reduced HDL cholesterollevels. 34-36 Clozapine and olanzapine havebeen most commonly associated with theseeffects which tend to correlate with increasedweight or BMI. 34-36 For patients who areoverweight, it is especially important toconsider the choice of anti psychotic tominimize an increase in weight and potentialsubsequent dyslipidemic effects.Orthostatic hypotensionOrthostatic hypotension can be an adverseeffect with serious consequences in anelderly person, potentially leading to fallsand fractures. Orthostatic hypotension ismore commonly seen with clozapine andquetiapine, but less so with risperidone andolanzapine. 37 Many of the typical antipsychotics(e.g., chlorpromazine) are alsoassociated with orthostatic hypotension. 37Patients who are concurrently treated withantihypertensive medications or who haveconditions that can increase their risk offalls (e.g., PD) should be monitored carefully.They should also be counselled onstrategies to minimize the impact of orthostatichypotension, 37 including getting upslowly from a sitting or lying position, drinkingan adequate amount of fluids, limitingtheir alcohol consumption, exercising regularly,avoiding long periods of standing, andsleeping with the head of the bed raised. 38SedationSedation, a common adverse effect of antipsychoticsseen more frequently with agentswith a high affinity for H 1receptors, can bea concern with clozapine, olanzapine andquetiapine, but less so with risperidone. 37Often, the sedating effects of these medicationscan account for the initial improvementsin behaviour. 37 If highly sedatinganti psychotics are used, patients should beadvised to take the medication at supper orbedtime unless daytime BPSD symptomsare severe. In some elderly patients withconcurrent insomnia, a sedating antipsychoticwould be a reasonable choice. 37ceAntipsychotic use in the elderlyce lessonPharmacy Practice national continuing education programStrokeWarnings from Health Canada about therisk of cerebrovascular accidents with useof risperidone and olanzapine haveprompted further investigation byresearchers. 39,40 A retrospective, population-basedcohort study conducted inOntario from 1997–2002 compared therisk of stroke in 11,400 patients ≥ 65years of age, among those prescribedtypical anti psychotics versus those takingolanzapine or risperidone. The authorsfound that the risk of stroke among usersof typical versus atypical anti psychoticswas not statistically significant. However,the study was limited by the inability tocontrol for some stroke risk factors andto account for transient ischemic attacksand mild strokes for which patients werenot hospitalized. 41Other data support the increased riskof stroke in patients taking atypical antipsychoticscompared to placebo. A metaanalysisof four clinical trials that evaluatedcardiovascular risks with risperidoneuse in elderly patients with dementiafound that there was approximately a threetimes higher risk of stroke in the treatmentgroups than with placebo. 42Older patients are already at higherrisk of stroke, so it is imperative thatantipsychotic use is approached cautiouslyand that stroke prevention strategies (e.g.lifestyle changes, controlling hypertension)are implemented. 43Increased mortality riskA 2005 Health Canada Advisory warnedthat atypical anti psychotics were associatedwith a 60% increased risk of allcausemortality as seen in a pooled analysisof thirteen randomized controlledtrials in elderly people with dementia takingrisperidone, olanzapine, and quetiapineor placebo. 44 The most commoncauses of death were heart failure, suddencardiac death or infections (e.g., pneumonia).Health Canada recommended labellingchanges for atypical anti psychoticsto reflect warning of this risk. 44A retrospective cohort study in the U.S.NOWFREE!of 22,890 patients ≥ 65 years of age usinganti psychotic medications found thatthere was a similar risk of death in thispopulation with the use of typical andatypical anti psychotics. The authors foundthat risk of death was highest shortly afterinitiation of therapy and in patients onhigher doses of typical anti psychotics.The authors did not know the causes ofdeath, but they did suggest that anticholinergiceffects (leading to changes inblood pressure and heart rate), prolongationof the QT interval (leading to conductiondelays) and EPS (leading to swallowingdifficulties) be further studied aspotential causes. 45In a cohort study that used healthcareutilization data for 37,241 British Columbiaresidents ≥ 65 years of age withoutcancer who took an anti psychotic medicationbetween 1996 and 2004, investigatorscompared 180-day all-cause mortalitybetween users of atypical and typical antipsychotics.In this study, patients takingtypical anti psychotics had a 32% higherdose-dependent risk of death compared tothose on an atypical anti psychotic. 46Drug interactionsIt is important to be aware of some of themore common drug interactions with antipsychoticagents.Anti psychotics that cause sedation mayinteract with other central nervous systemdepressant medications (such as certainanalgesics, antihistamines and anxiolytics).Co-administration of anticonvulsantswith anti psychotics may reduce plasmalevels of the anti psychotic, likely as a resultof hepatic enzyme induction by the anticonvulsant.This could result in higherlevels of anti psychotic if the anticonvulsantis discontinued. Anti psychotics can interactwith anticholinergic medications orthose with anticholinergic side effects (e.g.diphenhydramine, amitriptyline) resultingin a greater likelihood of side effects. 3,9,47The pharmacist’s roleWhen using anti psychotics in the elderly,pharmacists should note that lower dosagesanswer online at pharmacygateway.caseptember 2008 | pharmacypractice CE5

ce lessonNOWFREE!Pharmacy Practice national continuing education programAntipsychotic use in the elderlymay be required and that drug interactionsand adverse effects may be more likely tooccur in this population compared toyounger adults. 9 Pharmacists should ensurethat a patient’s risk factors are assessedsince caution is advised in patients withvascular or mixed dementia, history ofstroke or TIA, hypertension, diabetes, atrialfibrillation and smoking. 44An important principle of pharmaceuticalcare involves consideration of treatmentoutcomes. When treating an elderly patientwith an anti psychotic medication, the pharmacistshould be aware of expected outcomesand the time frame during whichre-evaluation of therapy and/or dose shouldoccur. When evaluating outcomes, it isimportant to have documentation by a caregiverof specific behaviours and their occurrence.It can take anywhere from severaldays up to two to four weeks to see the effectof the anti psychotic, so an adequate trialshould be in the range of two to four weeks. 9If the treatment is not effective, it should betapered, eventually discontinued and analternate treatment may be tried. If it iseffective, it should be reviewed on a regularbasis, approximately every twelve weeks.For BPSD it is advised to consider decreasingor discontinuing the anti psychotic everythree months if behaviours are stable. 48Ballard et al found that 67% of patients withdementia who had stable behaviours andhad received more than three months oftherapy with an anti psychotic experiencedno deterioration of symptoms when themedication was discontinued. 49Pharmacists should note that specificmonitoring parameters include changes insymptom severity and frequency, overallfunctioning, quality of life, and impressionsof caregivers and the patient, if possible.47 Also, monitoring for adverse effectsshould include evaluation of any signs ofEPS, and changes in blood pressure,weight, blood glucose and lipid levels. 47In the selection of an anti psychotic forany indication for an elderly person, pharmacistscan provide important informationabout the different adverse effect profiles ofanti psychotics to physicians and otherhealthcare providers. Features of individualagents (e.g., receptor affinities, adverseeffect profiles, efficacy) should be consideredwhen choosing specific medication.The lowest possible dose of an effectiveagent should be used for the shortest possibletime in patients with dementia. 47Patients and/or caregivers should be educatedabout what to expect with antipsychotictherapy, the potential risks, andhow treatment will be monitored. Pharmacistsshould ensure the patient and/or familyand caregivers are aware of the risks andbenefits of treatment with anti psychotics.Pharmacists can play an important role inproviding this information and engaging indialogue with patients and/or caregivers.SummaryIn the elderly population, anti psychoticsare most commonly used to treat BPSD.Pharmacists play an important role ineducating patients, caregivers and familyabout the risks and benefits of using thesemedications, as well as ensuring thatappropriate monitoring is done to ensureefficacy and safety. ppReferences1. Rapoport M, Mamdani M, Shulman KI, et al.Antipsychotic use in the elderly: shifting trends andincreasing costs. Int J Geriatr Psychiatry 2005;20:749-53.2. Hagen B, Esther CA, Ikuta R, et al. Antipsychotic druguse in Canadian long-term care facilities: prevalence,and patterns following resident relocation. Int Psychogeriatrics2005;17:179-93. 3. Neil W, Curran S, Wattis J.Antipsychotic prescribing in older people. Age and Ageing2003;32:475-83. 4. Seeman P. Atypical antipsychotics:mechanism of action. Can J Psychiatry 2002;47(1):27-38.5. Nassisi D, Korc B, Hahn S, et al. The evaluation andmanagement of the acutely agitated elderly patient. MountSinai J of Med 2006;73(7):976-84. 6. Work Group onAlzheimer’s Disease and Other Dementias. Practiceguideline for the treatment of patients with Alzheimer’sdisease and other dementias. 2nd edition. October 2007.American Psychiatric Association. www.psych.org/psych_pract/treatg/pg/alzpg/101007.pdf (accessed January 26,2008). 7. Conn DK. Management of psychosis andaggression associated with dementia. Journal of GeriatricCare 2002;1(2):129-40. 8. Schneider LS, Tariot PN,Dagerman KS, et al. Effectiveness of atypical antipsychoticdrugs in patients with Alzheimer’s disease. N Engl J Med2006;355:1525-38. 9. Herrmann N. Recommendations forthe management of behavioral and psychologicalsymptoms of dementia. Can J Neurol Sci 2001;28(suppl 1):S96-S107. 10. Alexopoulos GS, Streim JE, Carpenter D,et al. Using antipsychotic agents in older patients:Expert consensus panel for using antipsychotic drugs inolder patients. J Clin Psychiatry 2004;65(suppl 2):5-99.11. Omelan C. Approach to managing behaviouraldisturbances in dementia. Can Fam Physician2006;52:191-99. 12. French Clozapine Parkinson StudyGroup. Clozapine in drug-induced psychosis in Parkinson’sdisease. Lancet 1999;353:2041-2. 13. Parkinson StudyGroup. Low-dose clozapine for the treatment of druginducedpsychosis in Parkinson’s disease. N Engl J Med1999;340:757-63. 14. Pollak P, Tison F, Rascol O, et al.Clozapine in drug-induced psychosis in Parkinson’sdisease: a randomized, placebo-controlled studywith open follow-up. J Neurol Neurosurg Psychiatry2004;75:689-95. 15. Breier A, Sutton VK, Feldman PD, etal. Olanzapine in the treatment of dopamimetic-inducedpsychosis in patients with Parkinson’s disease. BiolPsychiatry 2002;52:438-45. 16. Ondo WG, Levy JK,Vuong KD, et al. Olanzapine treatment for dopaminergicinducedhallucinations. Mov Disord 2002;17:1031-1035.17. Ondo WG, Tintner R, Vuong KD, et al. Double-blind,placebo-controlled, unforced titration parallel trial ofquetiapine for dopaminergic-induced hallucinationsin Parkinson’s disease. Mov Disord 2005;20:958-63.18. Ondo WG, Tintner R, Vuong KD, et al. Double-blind,placebo-controlled, unforced titration parallel trial ofquetiapine for dopaminergic-induced hallucinationsin Parkinson’s disease. Mov Disord 2005;20:958-63.19. Rabey JM, Prokhorov T, Miniovitz A, et al. Effect ofquetiapine in psychotic Parkinson’s disease patients: adouble-blind labeled study of 3 months’ duration. MovDisord 2007;22:313-8. 20. Lewy body dementia. AlzheimerSociety of Canada. www.alzheimer.ca/english/disease/dementias-lewy.htm. (accessed May 15, 2008). 21. FrankC. Dementia with Lewy bodies. Review of diagnosis andpharmacological management. Can Fam Physician2003;49:1304-1311. 22. McKeith IG, Dickson DW, Lowe Jet al. Diagnosis and management of dementia with Lewybodies: third report of the dementia with Lewy bodiesconsortium. Neurology 2005;65(12):1863-72. 23. Gareri P,De Fazio P, Stilo M, et al. Conventional and atypicalantipsychotics in the elderly. 2003. www.medscape.com/viewarticle/457366. (accessed January 4, 2008) 24. LeuchtS, Wahlbeck K, Hamann J, et al. New generationantipsychotics versus low-potency conventionalantipsychotics: a systematic review and meta-analysis.Lancet 2003;361:1581-9. 25. Gardner DM, BaldessariniRJ and Waraich P. Modern antipsychotic drugs: a criticalreview. CMAJ 2005;172(12):1703-11. 26. Praharaj SK,Arora M. Amitriptyline for clozapine-induced nocturnalenuresis and sialorrhea. Br J Clin Pharmacology2007;63(1):128-129. 27. Richelsen E. Preclinicalpharmacology of neuroleptics: focus on new generationcompounds. J Clin Psychiatry 1996;57(suppl 11):4-11.28. Kumar V, Brecher M. Psychopharmacology of atypicalantipsychotics and clinical outcomes in elderly patients.J Clin Psychiatry 1999;60(suppl 13):5-9. 29. Tschoner A,Engl J, Laimer M, et al. Metabolic side effects ofantipsychotic medication. Int J Clin Pract 2007;61(8):1356-1370. 30. Hester EK, Thrower MR. Current options in themanagement of olanzapine-associated weight gain. AnnPharmacother 2005. www.theannals.com/cgi/content/abstract/aph.1D423v1?etoc. (accessed February 1, 2008).31. Sernyak MJ, Leslie DL, Alarcon RD, et al. Associationof diabetes mellitus with use of atypical neuroleptics inthe treatment of schizophrenia. Am J Psychiatry 2002;159:561-566. 32. Cohen D. Atypical antipsychotics and newonset diabetes mellitus. An overview of the literature.Pharmacopsychiatry 2004;37:1-11. 33. Consensusdevelopment conference on antipsychotic drugs andobesity and diabetes. Diabetes Care, February 2004.http://care.diabetesjournals.org/cgi/reprint/27/2/ 596?maxtoshow=&HITS=10&hits=10&RESULTFORMAT=&fulltext=weight+gain+and+atypical+antipsychotics&andorexactfulltext=and&searchid=1&FIRSTINDEX=0&sortspec=relevance&resourcetype=HWCIT. (accessed February 1, 2008).34. Wirshing DA, Boyd JA, Meng LR, et al. The effectsof novel antipsychotics on glucose and lipid levels. J ClinPsychiatry 2002;63:856-65. 35. Koro CE, Fedder DO,L’Italien GJ, et al. An assessment of the independenteffects of olanzapine and risperidone exposure on therisk of hyperlipidemia in schizophrenic patients. ArchGen Psychiatry 2002;59:1021-6. 36. Rettenbacher MA,Ebenbichler C, Hofer A, et al. Early changes of plasmalipids during treatment with atypical antipsychotics. IntClin Psychopharmacol 2006;21:369-72. 37. Casey DE.The relationship of pharmacology to side effects. J ClinPsychiatry 1997;58(suppl 10):55-62. 38. Orthostatichypotension. Merck Manual Online. www.merck.com/CE6 pharmacypractice | september 2008answer online at pharmacygateway.ca

mmpe/sec07/ch069/ch069d.htm 4. (accessed May 14,2008) 39. Health Canada. Important drug safetyinformation: Risperidal* (risperidone) and cerebrovascularadverse events in placebo-controlled dementia trials -Janssen-Ortho Inc. http://www.hc-sc.gc.ca/dhp-mps/medeff/advisories-avis/prof/2002/risperdal_hpc-cps_e.htmlOctober 2002 (accessed February 20, 2008). 40. HealthCanada. Zyprexa* (olanzapine) and cerebrovascularadverse events in placebo-controlled elderly dementiatrials. March 2004. http://www.hc-sc.gc.ca/dhp-mps/medeff/advisories-avis/prof/2004/zyprexa_hpc-cps_e.html(accessed February 20, 2008). 41. Herrmann N, MamdaniM, Lanctot KL. Atypical antipsychotics and risk ofcerebrovascular accidents. Am J Psychiatry 2004;161:1113-5. 42. Medicines and Healthcare ProductsRegulatory Agency (UK). Atypical antipsychotic drugsand stroke. March 2004. www.mhra.gov.uk/home/ceAntipsychotic use in the elderlyce lessonPharmacy Practice national continuing education programidcplg?IdcService=GET_FILE&dDocName=con019490&RevisionSelectionMethod=Latest (accessed January 12,2008). 43. Heart and Stroke Foundation. www.heartandstroke.com/site/c.ikIQLcMWJtE/b.3483933/k.CD67/Stroke.htm. (accessed May 30, 2008). 44. HealthCanada Advisory, 2005. http://www.hc-sc.gc.ca/dhp-mps/alt_formats/hpfb-dgpsa/pdf/medeff/atyp-antipsycho_hpc-NOWFREE!cps_e.pdf (accessed December 18, 2007). 45. Wang PS,Schneeweiss S, Avorn J, et al. Risk of death in elderlyusers of conventional vs. atypical antipsychoticmedications. N Engl J Med 2005;353(22):2355-61.46. Schneeweiss S, Setoguchi S, Brookhart A, et al. Riskof death associated with the use of conventional versusatypical antipsychotic drugs among elderly patients. CMAJ2007;176(5):627-32. 47. Jeste DV, Blazer D, Casey D, et al.ACNP white paper: update on use of antipsychotic drugsin elderly persons with dementia. Neuropsychopharmacology2007;1-14. 48. Ballard CG, Thomas A, Fossey J, et al.A 3-month randomized, placebo-controlled neurolepticdiscontinuation study in 100 people with dementia: theneuropsychiatric inventory median cutoff is a predictorof clinical outcome. J Clin Psychiatry 2004;65:1114-9.49. Goldstein JM. The new generation of antipsychoticdrugs; how atypical are they? Int J Neuropsychopharmacol2000;3:339-49. 50. Robinson DS. Antipsychotics:pharmacology and decision-making. Primary Psychiatry2007;14(10):23-25. www.primarypsychiatry.com/aspx/articledetail.aspx?articleid=1272. (accessed January 10,2008). 51. Schmidt AW, Lebel LA, Howard HR et al.Ziprasidone: a novel antipsychotic agent with a uniquehuman receptor binding profile. Eur J Pharmacol2001;425(3):197-201. 52. Tandon R. Introduction.Supplement on ziprasidone. Br J Clin Pharmacol2000;49(S1):1S-3S.QuestionsTo answer online, go to www.pharmacygateway.ca, CE section, CE Online, Pharmacy Practice1 K.M. is an 86-year-old female resident ofan LTCF. She has Alzheimer’s disease and wasadmitted to the facility when her husbandbegan to have a difficult time at home with her.She began to wander and was at risk of becominglost after leaving the home. At the facility,her wandering became a problem for the staffand other residents. Her nurse has asked youwhich antipsychotic medication would be bestfor her. Which of the following is correct?a) She should be given an atypical antipsychotic asthere is more evidence of their effectiveness inbehaviour disturbances such as wandering, comparedto typical antipsychotics.b) K.M.’s physician should prescribe a low dose ofrisperidone because it is available in liquid formand the dose can slowly be titrated.c) Olanzapine has been shown to be more effectivethan risperidone for wandering, so this is the bestoption in K.M.’s case.d) Unless K.M. has other behavioural disturbancessuch as aggressive behaviour or is dangerous toherself or others, no antipsychotic is indicatedfor treatment of her wandering.2 Which of the following antipsychotics isthe least likely to cause orthostatic hypotensiondue to receptor binding activity?a) haloperidol d) chlorpromazineb) risperidone e) clozapinec) quetiapine3 P.D. is a 75-year-old male with depressionwho was prescribed risperidone liquid a fewmonths ago as an adjunct to sertraline. Recently,his dose of risperidone was increased to 2 mgBID. His wife has noted some unusual new symptoms,including strange facial expressions andunexpected movements of his arms. Which ofthe following is the most likely explanation?a) P.D. has developed Parkinson’s disease due torisperidone.b) P.D. has developed tardive dyskinesia due torisperidone.c) P.D. has developed akathisia due to risperidone.d) P.D. has had an allergic reaction to risperidone.e) P.D. does not like the taste of the risperidoneliquid.4 J.N. is a 78-year-old female living in a retirementhome. She has Parkinson’s disease and isbeing treated with levodopa/carbidopa. J.N. hashad a history of falls and has somewhat limitedmobility. She is currently taking ramipril 5 mgdaily, levodopa/carbidopa 100/25 2 tablets TID,and was recently prescribed quetiapine 25 mgdaily for hallucinations. Which of the following iscorrect about her medication therapy?a) Quetiapine has been shown to worsen symptomsin Parkinson’s disease.b) J.N. may be at risk of orthostatic hypotension soshould be advised how to minimize the risk offalls.c) Quetiapine has been shown to be more effectivethan clozapine in treating Parkinson’s diseaserelatedpsychotic symptoms.d) J.N. should be prescribed an antipsychotic withhigher anticholinergic effects to help treat herParkinson’s disease symptoms.e) None of the above.5 Which of the following is true regardingdiabetes and antipsychotics?a) All patients on atypical antipsychotics shouldhave a baseline fasting plasma glucose level.b) The most commonly implicated agents associatedwith diabetes are clozapine and quetiapine.c) New onset diabetes generally does not occuruntil about three months after antipsychotictherapy has been initiated.d) Hyperglycemia associated with antipsychotics isirreversible.e) All of the above.6 Y.R. is a 70-year-old female with dementiataking olanzapine. Y.R. has always been overweight.Aside from therapeutic outcomes ofher treatment, what else should be part of themonitoring regimen for Y.R.’s treatment?a) monitoring for agranulocytosisb) lipid profile because of her current weight andhealth risks, in addition to the added risk ofdyslipidemia with olanzapinec) agitation because this is a potential adverse effectof olanzapined) blood glucose monitoring due to the risk ofdiabetes with olanzapinee) both b) and d)7 Which of the following is true with respectto antipsychotic use and patients with dementiawith Lewy bodies (DLB)?a) All antipsychotics can cause serious side effectsin people with DLB.b) Sensitivity to antipsychotics occurs in about 10%of patients with DLB.c) Sensitivity to antipsychotics in patients with DLBcan lead to autonomic symptoms like neuro lepticmalignant syndrome.d) a) and c)e) All of the above.8 V.P. is an 82-year-old female with dementiawho is taking quetiapine 25 mg TID forexcessive agitation. V.P. continues to be quiteagitated throughout the day. She is alsoextremely fatigued, which makes it difficultfor her to perform activities of daily living.Which of the following recommendationswould best minimize these problems?a) Switch to risperidone to minimize sedation.b) Switch to clozapine to minimize sedation.c) Reduce her quetiapine dose to minimizesedation.d) Consider discontinuing quetiapine since her agitationdoes not appear to be responding to it.9 Which of the following is true of antipsychoticuse for patients with dementia?a) Antipsychotics are indicated for the treatment ofanxiety associated with dementia.b) Antipsychotics with greater anticholinergic effectsshould be avoided in patients with dementia.c) Antipsychotics should be re-evaluated annuallyin patients with BPSD.d) Atypical antipsychotics are more effective thantypical agents for behavioural disturbances inpatients with dementia.e) None of the above.10 M.F. is a 78-year-old female with dementiawho lives in a nursing home. She has beenquite anxious and has had difficulty sleeping.Her physician has prescribed quetiapine 25 mgat bedtime to help manage her symptoms.Which of the following is true of her therapy?a) A more appropriate starting dose of quetiapinewould be 100 mg for this patient.answer online at pharmacygateway.caseptember 2008 | pharmacypractice CE7

ce lessonNOWFREE!QuestionsThis monthAntipsychotic use in the elderlyPharmacy Practice national continuing education programAntipsychotic use in the elderlyb) Quetiapine is an appropriate therapy for hersymptoms, especially since she is having troublesleeping.c) Her care team should attempt to assess what iscausing her anxiety and look at alternativemethods to manage insomnia.d) She should receive quetiapine therapy indefinitelybecause dementia is a progressive condition.e) None of the above.11 Which of the following is true about theuse of antipsychotics for elderly patients withdelirium?a) It is appropriate in most cases to use antipsychoticsfor the short term to treat delirium.b) Antipsychotics are used to treat behavioural andnon-behavioural symptoms of delirium.c) Antipsychotics with a high propensity for anticholinergiceffects, as well as other anticholinergicmedications, should be avoided because theycan contribute to confusion in delirium.d) Both a) and c).e) None of the above.12 D.J. is an 80-year-old male with Alzheimer’sdisease who lives in an LTCF. He has beentaking olanzapine 5 mg for 12 months for themanagement of his behavioural problems,including aggressive behaviour. His caregiverhas noticed new symptoms including facialgrimaces and lip smacking. Which of the followingis/are true regarding D.J.’s case?a) Olanzapine is not likely to cause EPS, so his newsymptoms are probably not due to this sideeffect.b) Assuming D.J. is not dangerous to himself or others,he has been taking olanzapine long enoughfor his physician to attempt to discontinue it.c) D.J. may be experiencing akathisia due to olanzapine.d) D.J.’s physician should discontinue the olanzapineand start risperidone as it is less likely tocause the side effects he is experiencing.e) Both b) and c).13 For which of the following behavioursassociated with dementia in the LTCF residentare antipsychotics considered appropriate?ce facultyAuthorRosemarie Patodia, BScPhm, CGP, has been aCertified Geriatric Pharmacist for 10 years and haspractised in hospital, community long-term careand retail pharmacy settings. She has developedand taught geriatric pharmacotherapy programs forpharmacists in her past role at Shoppers Drug Martand for the Ontario Pharmacists’ Association. Shehas published many continuing education articlesand has spoken on several senior care-related topicsover the course of her career.To answer online, go to www.pharmacygateway.ca, CE section, CE Online, Pharmacy Practicea) shouting out at inappropriate timesb) walking in and out of other residents’ roomsc) psychotic behaviours (e.g. hallucinations)d) anxietye) a), b) and c)14 V.F. has been diagnosed with Lewy bodydementia. He is experiencing delusions thatrequire treatment. Which of the following recommendationsis the most appropriate withregard to his medication therapy?a) He will respond better to an atypical antipsychoticthan to a typical antipsychotic.b) Haloperidol is a good choice for treatment of hisdelusions.c) Low-dose quetiapine is likely to be a safe andeffective option to treat his symptoms.d) Antipsychotics are contraindicated in patientswith Lewy body dementia with delusions.e) None of the above.15 Which of the following is/are a considerationwith respect to antipsychotic use in theelderly patient?a) Lipid-soluble antipsychotics are not likely toaccumulate in an older person, so they are a goodchoice in this population.b) Risperidone can have a more pronounced effectin an older person because of reduced proteinbinding.c) Excessive sedation can be a risk associated withantipsychotics with high affinity for histaminicreceptors.d) High-potency antipsychotics should be avoidedin dementia because of their high likelihood ofcausing anticholinergic effects.e) Both b) and c)16 Which antipsychotic is least likely to causeanticholinergic effects?a) risperidone d) olanzapineb) clozapine e) ziprasidonec) chlorpromazine17 J.B. is a 75-year-old male with a historyof CVA (cerebrovascular accident), Alzheimer’sdisease, insomnia, dyslipidemia and hypertension.He is currently being treated withAll lessons are reviewed by a minimum of sixpharmacists for accuracy, currency and relevanceto current pharmacy practice.This lesson is valid until July 28, 2011. Informationabout antipsychotic use in the elderly may changeover the course of this time. Readers are responsiblefor determining the most current aspects of this topic.CE Clinical EditorBrenda McBean Cochran, B.S.P., M.Sc.(Phm)Pharmacist consultant, Bedford, N.S.Continuing Education Project ManagerSheila McGovern, Toronto, Ont.ramipril, acetylsalicylic acid, rosuvastatin, andlorazepam at night. He has begun to shoutobscenities and has attempted to hit a numberof people around him. Which of the followingwould be a good therapeutic choice to helpmanage these symptoms?a) chlorpromazineb) quetiapinec) Either of the above would be a good therapeuticchoice.d) None of the antipsychotics would be a goodtherapeutic choice.18 S.L. is an 80-year-old female patient takingolanzapine for the past few months for paranoiaassociated with Parkinson’s disease. Hermovement-related symptoms of Parkinson’sdisease are generally well-controlled. Whichof the following is/are an important part of thepharmacist’s monitoring plan for S.L.?a) changes in her paranoia symptomsb) changes in her Parkinson’s symptoms, especiallyat higher doses of olanzapinec) changes in her blood pressured) both a) and b)e) all of the above19 When treating elderly patients who havedementia with antipsychotic therapy, whichof the following should be considered withrespect to dosing?a) The dose of an antipsychotic should be titratedslowly to minimize side effects.b) Patients with BPSD who have sporadic behaviouralsymptoms should be given low doses ofantipsychotics on an “as needed” basis.c) Lower doses of antipsychotics are more oftenrequired in elderly patients than in youngerpatients.d) Both a) and c).e) All of the above.20 A patient taking an antipsychotic and ananticonvulsant may experience higher levelsof the antipsychotic if the anticonvulsant isdiscontinued.a) true b) falseCE MANAGING EDITORRosalind Stefanacrosalind.stefanac@pharmacygroup.rogers.comThis lesson is published by Rogers Publishing Ltd.,One Mount Pleasant Rd., 7th floor, Toronto, ON M4Y 2Y5.Editorial office: Tel: (416) 764-3927 Fax: (416) 764-3931.CE queries: Tel: (416) 764-3879 Fax: (416) 764-3937mayra.ramos@rci.rogers.com. No part of this CE lessonmay be reproduced, in whole or in part, without thewritten permission of the publisher.The author, expert reviewers and provider state that theyhave no real or potential conflict to disclose. This lesson issupported by an unrestricted grant from Mylan.CE8 pharmacypractice | september 2008answer online at pharmacygateway.ca

To answer this CE lesson onlineIf currently logged into our Online Ce Program, please return to the “LessonsAvailable Online” Page and click on “Link to questions” for this CE Lesson.If not logged in but already registered to our Online Ce Program, pleaseclick here:http://ce.pharmacygateway.com/Pharmacy/login/index.aspIf you have not registered for our Online Ce Program and wish to answer online,please click here: http://ce.pharmacygateway.com/Pharmacy/login/adduser.aspIf you have any questions please contact:Mayra RamosPharmacy Practice, Pharmacy Post, Drugstore Canada, Novopharm CE Series,More CCCEP-approved CEs or Tech Talk CEs (English and French)Fax: (416) 764-3937Email: mayra.ramos@rci.rogers.comFrancine BeauchampQuebec Pharmacie and L’actualite PharmaceutiqueFax: (514) 843-2183Email: francine.beauchamp@rci.rogers.com